Rimantadine Hydrochloride (2 brand names, 2 dosage forms, 1 route)
Available dosage forms: TABLET, SYRUP.
Routes of administration: ORAL.
Brand Names
- FLUMADINE
- RIMANTADINE HYDROCHLORIDE
Indications and Usage
Rimantadine hydrochloride tablet is indicated for the prophylaxis and treatment of illness caused by various strains of influenza A virus in adults (17 years and older). Rimantadine hydrochloride tablet is indicated for prophylaxis against influenza A virus in children (1 year to 16 years of age).
Contraindications
Rimantadine hydrochloride tablet is contraindicated in patients with known hypersensitivity to drugs of the adamantane class, including rimantadine and amantadine.
Adverse Reactions
In 1,027 patients treated with rimantadine hydrochloride in controlled clinical trials at the recommended dose of 200 mg daily, the most frequently reported adverse events involved the gastrointestinal and nervous systems. Incidence >1%: Adverse events reported most frequently (1 % to 3%) at the recommended dose in controlled clinical trials are shown in the table below. Rimantadine (n=1,027) Control (n=986) Nervous System Insomnia 2.1% 0.9% Dizziness 1.9% 1.1% Headache 1.4% 1.3% Nervousness 1.3% 0.6% Fatigue 1.0% 0.9% Gastrointestinal System Nausea 2.8% 1.6% Vomiting 1.7% 0.6% Anorexia 1.6% 0.8% Dry mouth 1.5% 0.6% Abdominal Pain 1.4% 0.8% Body as a Whole Asthenia 1.4% 0.5% Less frequent adverse events (0.3 to 1%) at the recommended dose in controlled clinical trials were: Gastrointestinal System: diarrhea, dyspepsia; Nervous System: impairment of concentration, ataxia, somnolence, agitation, depression; Skin and Appendages: rash; Hearing and Vestibular: tinnitus; Respiratory: dyspnea. Additional adverse events (less than 0.3%) reported at recommended doses in controlled clinical trials were: Nervous System: gait abnormality, euphoria, hyperkinesia, tremor, hallucination, confusion, convulsions; Respiratory: bronchospasm, cough; Cardiovascular: pallor, palpitation, hypertension, cerebrovascular disorder, cardiac failure, pedal edema, heart block, tachycardia, syncope; Reproduction: non-puerperal lactation; Special Senses: taste loss/change, parosmia. Rates of adverse events, particularly those involving the gastrointestinal and nervous systems, increased significantly in controlled studies using higher than recommended doses of rimantadine hydrochloride. In most cases, symptoms resolved rapidly with discontinuation of treatment. In addition to the adverse events reported above, the following were also reported at higher than recommended doses: increased lacrimation, increased micturition frequency, fever, rigors, agitation, constipation, diaphoresis, dysphagia, sto
Drug Interactions
Acetaminophen: Rimantadine hydrochloride, 100 mg, was given twice daily for 13 days to 12 healthy volunteers. On day 11, acetaminophen (650 mg four times daily) was started and continued for 8 days. The pharmacokinetics of rimantadine were assessed on days 11 and 13. Co-administration with acetaminophen reduced the peak concentration and AUC values for rimantadine by approximately 11%. Aspirin: Rimantadine hydrochloride, 100 mg, was given twice daily for 13 days to 12 healthy volunteers. On day 11, aspirin (650 mg, four times daily) was started and continued for 8 days. The pharmacokinetics of rimantadine were assessed on days 11 and 13. Peak plasma concentrations and AUC of rimantadine were reduced approximately 10% in the presence of aspirin. Cimetidine: When a single 100 mg dose of rimantadine hydrochloride was administered with steady-state cimetidine (300 mg four times a day), there were no statistically significant differences in rimantadine Cmax or AUC between rimantadine hydrochloride alone and rimantadine hydrochloride in the presence of cimetdine. Live Attenuated Influenza Vaccine (LAIV): The concurrent use of rimantadine hydrochloride with live attenuated intranasal influenza vaccine has not been evaluated. However, because of potential interference between these products, the live attenuated intranasal influenza vaccine should not be administered until 48 hours after cessation of rimantadine hydrochloride and rimantadine hydrochloride should not be administered until two weeks after the administration of live attenuated intranasal influenza vaccine unless medically indicated. The concern about potential interference arises principally from the potential for antiviral drugs to inhibit replication of live vaccine virus.
Mechanism of Action
The mechanism of action of rimantadine is not fully understood. Rimantadine appears to exert its inhibitory effect early in the viral replicative cycle, possibly inhibiting the uncoating of the virus. Genetic studies suggest that a virus protein specified by the virion M2 gene plays an important role in the susceptibility of influenza A virus to inhibition by rimantadine.
Overdosage
As with any overdose, supportive therapy should be administered as indicated. Overdoses of a related drug, amantadine, have been reported with adverse reactions consisting of agitation, hallucinations, cardiac arrhythmia and death. The administration of intravenous physostigmine (a cholinergic agent) at doses of 1 to 2 mg in adults (Ref. 7) and 0.5 mg in children (Ref. 8) repeated as needed as long as the dose did not exceed 2 mg/hour has been reported anecdotally to be beneficial in patients with central nervous system effects from overdoses of amantadine.